Introduction & Objectives: Although anti-cancer treatments, including chemotherapy (CTs), targeted therapies (TTs), radiation therapy, and immunotherapy (ITs), effectively treat cancer, they can cause significant skin-related toxicities (AEs). These toxicities can lead to discomfort and therapy discontinuation. This study investigated these associations using a large dataset.
Materials & Methods: The study utilised the US FDA Adverse Reporting System (FAERS) dataset, focusing on Healthcare Professional reports between January 2013 − September 2022, encompassing 3,399,830 reports, 3,084 drugs, and 16,347 AEs. To minimise false positives, we employed a nearest-neighbour matching model on demographics and severity criteria and addressed the inflation of error rates due to the multiplicity of tests.
Results: We identified 146 marketed anti-cancer drugs in the database with at least 5 reports of skin AEs. Of the 2,757 drug-AE pairs, 708 displayed a significant reporting odds ratio (ROR) >1, involving 102 drugs and 135 skin AEs. Rash was significantly associated with 44 drugs and dry skin with 25 drugs. Methotrexate was significantly associated with 35 different AEs and anti-BRAF vemurafenib with 26 AEs. TTs were present in 57% of the pairs, CTs in 38%, and immune checkpoint blocking agents in 5%. Multikinase inhibitors were present in 15% of the pairs, followed by antimetabolites (14%).
Conclusion: This study used a large dataset to examine associations between cancer drugs and skin AEs. 146 anti-cancer drugs were found to have skin AEs, with rash and dry skin being the most reported AEs. TTs were most associated with skin AEs, followed by CTs. Methotrexate and vemurafenib had the most significant number of associations. These data don’t allow evaluation of skin AE incidence with anti-cancer drugs as they are probably under-reported, but the findings do emphasise the importance of monitoring skin AEs in patients exposed to anti-cancer treatments.